In recent years a substantial number of important new synthetic procedures have been developed utilizing organothallium intermediates. Carbonylation of arylthallium compounds should provide a useful, direct and simple method of synthesis of a wide variety of biologically active compounds such as the lactones, phthalides, as well as anhydrides such as phthalic anhydride. In addition, various phthalide derivatives have shown useful fungicidal, bacteriocidal, herbicidal and analgesic activity. Some have even been reported as useful in treating heart disease, while other derivatives show diuretic and hypotensive-hypertensive activity.
Until recently, most of the synthetic routes to these types of compounds started with the carboxylic acid, corresponding to the lactone-carbonyl group and then introduced an orthoside chain which rapidly lactonized. But the yields were unsatisfactory and oftentimes side reactions occurred. Also, many of the starting materials were not readily available.
Direct carbonylation of arylthallium compounds has been studied and reported. See for example, Davidson, J. M., et al., J. Chem. Soc. A. 1968, pp. 616-617. However, the procedure as reported requires very stringent conditions of high temperature and pressure; in particular pressures of from 90 to 250 atmospheres at temperatures of 75.degree. F. to 135.degree. F. And even then, the reported yields are quite low. It therefore can be seen that there is not currently a method for direct carbonylation of arylthallium compounds at moderate temperatures and pressures to provide a direct and convenient synthesis route for a wide variety of biologically active compounds, including phthalides, 3,4-dihydroisocoumarins, anhydrides such as phthalic anhydride, and the like.
This invention has as its primary object the fulfillment of this need. The manner of accomplishing this objective as well as others will become apparent from the detailed description of the invention which will follow hereinafter.